深部电刺激伏隔核对吗啡成瘾大鼠复吸后伏隔核内γ-氨基丁酸含量变化的影响

The effect of deep brain stimulation of bilateral nucleus accumbens in morphine-dependent rats to the change of GABA after relapses

目的研究深部电刺激(deep brain stimulation,DBS)双侧伏隔核对吗啡成瘾大鼠复吸后伏隔核内γ-氨基丁酸(γ-aminobutyric Acid,GABA)含量的影响。方法手术前使用条件性位置偏爱试验(conditionedplace preference,CPP)筛选无自然偏爱大鼠,随机分组后DBS组行电极植入术,术后10天采用固定剂量吗啡皮下注射(10mg.Kg-1)建立吗啡成瘾大鼠模型(使用CPP证实)。通过改进的DBS电路进行电刺激(频率130Hz,电流300uA,电压1V,1h.d-1),在不同的时间点使用CPP证实DBS组大鼠戒断成功后再皮下给予小剂量吗啡(3mg.Kg-1),24h后使用CPP验证吗啡成瘾大鼠复吸模型建立成功。CPP试验结束后于冰台上按大鼠脑立体定位图谱取伏隔核行高效液相色谱法(high performance liquid chromatography,HPLC)测定GABA含量。结果①皮下注射固定剂量吗啡能够使大鼠成瘾,DBS能够有效抑制吗啡复吸行为;②morphine+DBS组大鼠伏隔核内GABA含量与吗啡组,morphine+sham组差异明显。结论 DBS双侧伏隔核使吗啡成瘾大鼠复吸后伏隔核内GABA含量增加。

Objective To study the change of the content of GABA in the nucleus accumbens after the deep brain stimulation of bilateral nucleus accumbens in morphine-dependent rats after relapse.Methods CPP was used to screen the rats without natural place preference before the implantation of electrodes.After implantation,morphine hydrochloride was injected subcutaneously at fixed dose（10mg·Kg-1） to establish the model of morphine addicted rats.Modified electrical circuit was used to procedure the DBS（frequency 130Hz,current 300uA,voltage 1V,1h·d-1）,CPP test was used to verify withdrawn of morphine addicted rats.Then small dose of morphine（3mg·Kg-1） was injected subcutaneously to induce the relapse.HPLC was used to detect the content of GABA in the nucleus accumbens.Results ① Subcutaneous injection of morphine could induce the addiction of morphine in rats,while DBS could accelerate the process of withdrawn and prevent the relapse.②The content of GABA in nucleus accumbens in morphine＋DBS had significant difference compared with that in morphine and morphine＋sham.Conclusion Deep brain stimulation could increase the content of GABA in morphine-dependent rats.